Total serum N-glycans associate with response to immune checkpoint inhibition therapy and survival in patients with advanced melanoma

• Published in: BMC cancer Vol. 23; no. 1; pp. 166 - 12
• Main Authors: Visconti, Alessia, Rossi, Niccolò, Deriš, Helena, Lee, Karla A, Hanić, Maja, Trbojević-Akmačić, Irena, Thomas, Andrew M., Bolte, Laura A., Björk, Johannes R., Hooiveld-Noeken, Jahlisa S., Board, Ruth, Harland, Mark, Newton-Bishop, Julia, Harries, Mark, Sacco, Joseph J., Lorigan, Paul, Shaw, Heather M., de Vries, Elisabeth G.E., Fehrmann, Rudolf S.N., Weersma, Rinse K., Spector, Tim D., Nathan, Paul, Hospers, Geke A. P., Sasieni, Peter, Bataille, Veronique, Lauc, Gordan, Falchi, Mario
• Format: Journal Article
• Language: English
• Published: London BioMed Central 18.02.2023; BioMed Central Ltd; BMC
• Subjects: Ambulatory Care Facilities; Analysis; Biomarkers; Biomedical and Life Sciences; Biomedicine; Blood proteins; Cancer; Cancer Research; Cancer therapies; Care and treatment; Development and progression; Dosage and administration; Drug dosages; Enzymes; Europe; Glycoproteins; Glycosylation; Health aspects; Health Promotion and Disease Prevention; Humans; Immune Checkpoint Inhibitors; Immune response; Immunotherapy; Ipilimumab; Lipids; Magnetic resonance imaging; Medical prognosis; Medicine/Public Health; Melanoma; Melanoma - drug therapy; Metastases; Metastasis; N-glycans; Oncology; Patient outcomes; Patients; Polysaccharides; Prevention; Prostate cancer; Proteins; Receptor antibodies; Response; Response rates; Risk factors; Serum proteins; Skin cancer; Surgical Oncology; Survival; Tomography; Total serum N-glycomics; Tumors; Europe; United Kingdom; United Kingdom > UK; Netherlands; Response; Immune checkpoint inhibitors; Total serum; glycomics; Survival; Melanoma; Total serum N-glycomics
• ISSN: 1471-2407; 1471-2407
• DOI: 10.1186/s12885-023-10511-3

Background Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of melanoma and other cancers. However, no reliable biomarker of survival or response has entered the clinic to identify those patients with melanoma who are most likely to benefit from ICIs. Glycosylation affects proteins and lipids’ structure and functions. Tumours are characterized by aberrant glycosylation which may contribute to their progression and hinder an effective antitumour immune response. Methods We aim at identifying novel glyco-markers of response and survival by leveraging the N- glycome of total serum proteins collected in 88 ICI-naive patients with advanced melanoma from two European countries. Samples were collected before and during ICI treatment. Results We observe that responders to ICIs present with a pre-treatment N -glycome profile significantly shifted towards higher abundancy of low-branched structures containing lower abundances of antennary fucose, and that this profile is positively associated with survival and a better predictor of response than clinical variables alone. Conclusion While changes in serum protein glycosylation have been previously implicated in a pro-metastatic melanoma behaviour, we show here that they are also associated with response to ICI, opening new avenues for the stratification of patients and the design of adjunct therapies aiming at improving immune response.